A reduced concentration of serum testosterone resulting in male hypogonadism is a well described endocrine abnormality associated with classical signs and symptoms. This manuscript presents one such patient. However, low serum testosterone is being recognized more commonly associated with aging and chronic disease. It is in this situation in which the signs and symptoms of male hypogonadism can be subtle and non-specific. This manuscript reviews examples of such situations and highlights our need to have a reliable and accurate measure of serum testosterone. Both clinicians and researchers need better assays to better understand basic mechanisms, diagnose, treat, and monitor men with testosterone deficiency.